Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Clinical nutrition, enteral and parenteral nutrition

Immune-modulatory effect of probiotic Bifidobacterium lactis NCC2818 in individuals suffering from seasonal allergic rhinitis to grass pollen: an exploratory, randomized, placebo-controlled clinical trial



Probiotics are defined as ‘living micro-organisms that when administered in adequate amounts confer a health benefit to the host’. Different probiotic strains have been investigated for beneficial effects on allergic disorders. The purpose of the current study was to evaluate the effect of orally administering the probiotic Nestlé culture collection (NCC)2818 Bifidobacterium lactis strain on immune parameters and nasal symptom scores in subjects suffering from seasonal allergic rhinitis (SAR).


The study was a double-blinded, parallel, randomized placebo-controlled trial conducted during the peak of the pollen season. Adult subjects with clinical history of SAR and positive skin prick test to grass pollen were recruited. The subjects received B. lactis NCC2818 or placebo for 8 weeks and completed symptom questionnaires every week. Whole blood was collected at baseline (V1), 4 weeks (V2) and 8 weeks (V3) to measure immune parameters.


Concentrations of Th-2 cytokines, secreted by stimulated blood lymphocytes, were significantly lower in the probiotic group compared with the placebo group at V3 (interleukin (IL)-5, P=0.016; IL-13, P=0.005). Total nasal symptom scores were significantly lower in the second month of the study (weeks 5–8) in the probiotic group compared with the placebo group (P=0.03). Also, percentages of activated CD63 expressing basophils were significantly lower in the probiotic group at V2 (P=0.02).


Oral administration of the probiotic NCC2818 mitigates immune parameters and allergic symptoms during seasonal exposure. These promising results warrant that B. lactis NCC2818 be investigated further in large-scale trials for management of respiratory allergy.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5


  1. Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB et al. Allergic rhinitis and its impact on asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol 2010; 126: 466–476.

    Article  Google Scholar 

  2. Keil T, Bockelbrink A, Reich A, Hoffmann U, Kamin W, Forster J et al. The natural history of allergic rhinitis in childhood. Pediatr Allergy Immunol 2010; 21: 962–969.

    CAS  Article  Google Scholar 

  3. Passalacqua G, Ciprandi G . Novel therapeutic interventions for allergic rhinitis. Expert Opin Investig Drugs 2006; 15: 1615–1625.

    CAS  Article  Google Scholar 

  4. Stanaland BE . Therapeutic measures for prevention of allergic rhinitis/asthma development. Allergy Asthma Proc 2004; 25: 11–15.

    PubMed  Google Scholar 

  5. Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria. Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria 2001.

  6. Borchers AT, Selmi C, Meyers FJ, Keen CL, Gershwin ME . Probiotics and immunity. J Gastroenterol 2009; 44: 26–46.

    Article  Google Scholar 

  7. Ezendam J, van Loveren H . Probiotics: immunomodulation and evaluation of safety and efficacy. Nutr Rev 2006; 64: 1–14.

    Article  Google Scholar 

  8. Ruemmele FM, Bier D, Marteau P, Rechkemmer G, Bourdet-Sicard R, Walker WA et al. Clinical evidence for immunomodulatory effects of probiotic bacteria. J Pediatr Gastroenterol Nutr 2009; 48: 126–141.

    CAS  Article  Google Scholar 

  9. Boyle RJ, Tang ML . The role of probiotics in the management of allergic disease. Clin Exp Allergy 2006; 36: 568–576.

    CAS  Article  Google Scholar 

  10. Kalliomaki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E . Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 2001; 357: 1076–1079.

    CAS  Article  Google Scholar 

  11. Ouwehand AC . Antiallergic effects of probiotics. J Nutr 2007; 137: 794S–797S.

    CAS  Article  Google Scholar 

  12. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M et al. Diversity of the human intestinal microbial flora. Science 2005; 308: 1635–1638.

    Article  Google Scholar 

  13. Kalliomaki M, Isolauri E . Pandemic of atopic diseases–a lack of microbial exposure in early infancy? Curr Drug Targets Infect Disord 2002; 2: 193–199.

    CAS  Article  Google Scholar 

  14. Ivory K, Chambers SJ, Pin C, Prieto E, Arques JL, Nicoletti C . Oral delivery of Lactobacillus casei Shirota modifies allergen-induced immune responses in allergic rhinitis. Clin Exp Allergy 2008; 38: 1282–1289.

    CAS  Article  Google Scholar 

  15. Snel J, Vissers YM, Smit BA, Jongen JM, van der Meulen ET, Zwijsen R et al. Strain-specific immunomodulatory effects of Lactobacillus plantarum strains on birch-pollen-allergic subjects out of season. Clin Exp Allergy 2011; 41: 232–242.

    CAS  Article  Google Scholar 

  16. Tamura M, Shikina T, Morihana T, Hayama M, Kajimoto O, Sakamoto A et al. Effects of probiotics on allergic rhinitis induced by Japanese cedar pollen: randomized double-blind, placebo-controlled clinical trial. Int Arch Allergy Immunol 2007; 143: 75–82.

    Article  Google Scholar 

  17. Wang MF, Lin HC, Wang YY, Hsu CH . Treatment of perennial allergic rhinitis with lactic acid bacteria. Pediatr Allergy Immunol 2004; 15: 152–158.

    Article  Google Scholar 

  18. Wassenberg J, Nutten S, Audran R, Barbier N, Aubert V, Moulin J et al. Effect of Lactobacillus paracasei ST11 on a nasal provocation test with grass pollen in allergic rhinitis. Clin Exp Allergy 2011; 41: 565–573.

    CAS  Article  Google Scholar 

  19. Xiao JZ, Kondo S, Yanagisawa N, Takahashi N, Odamaki T, Iwabuchi N et al. Probiotics in the treatment of Japanese cedar pollinosis: a double-blind placebo-controlled trial. Clin Exp Allergy 2006; 36: 1425–1435.

    CAS  Article  Google Scholar 

  20. Xiao JZ, Kondo S, Yanagisawa N, Miyaji K, Enomoto K, Sakoda T et al. Clinical efficacy of probiotic Bifidobacterium longum for the treatment of symptoms of Japanese cedar pollen allergy in subjects evaluated in an environmental exposure unit. Allergol Int 2007; 56: 67–75.

    Article  Google Scholar 

  21. Xiao JZ, Kondo S, Yanagisawa N, Takahashi N, Odamaki T, Iwabuchi N et al. Effect of probiotic Bifidobacterium longum BB536 in relieving clinical symptoms and modulating plasma cytokine levels of Japanese cedar pollinosis during the pollen season. A randomized double-blind, placebo-controlled trial. J Investig Allergol Clin Immunol 2006; 16: 86–93.

    CAS  PubMed  Google Scholar 

  22. Kim JY, Kwon JH, Ahn SH, Lee SI, Han YS, Choi YO et al. Effect of probiotic mix (Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus) in the primary prevention of eczema: a double-blind, randomized, placebo-controlled trial. Pediatr Allergy Immunol 2010; 21: e386–e393.

    Article  Google Scholar 

  23. Isolauri E, Arvola T, Sutas Y, Moilanen E, Salminen S . Probiotics in the management of atopic eczema. Clin Exp Allergy 2000; 30: 1604–1610.

    CAS  Article  Google Scholar 

  24. Wickens K, Black PN, Stanley TV, Mitchell E, Fitzharris P, Tannock GW et al. A differential effect of 2 probiotics in the prevention of eczema and atopy: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 2008; 122: 788–794.

    Article  Google Scholar 

  25. Niers L, Martin R, Rijkers G, Sengers F, Timmerman H, van UN et al. The effects of selected probiotic strains on the development of eczema (the PandA study). Allergy 2009; 64: 1349–1358.

    CAS  Article  Google Scholar 

  26. Ocmant A, Peignois Y, Mulier S, Hanssens L, Michils A, Schandene L . Flow cytometry for basophil activation markers: the measurement of CD203c up-regulation is as reliable as CD63 expression in the diagnosis of cat allergy. J Immunol Methods 2007; 320: 40–48.

    CAS  Article  Google Scholar 

  27. Wolanczyk-Medrala A, Gogolewski G, Liebhart J, Gomulka K, Litwa M, Panaszek B et al. A new variant of the basophil activation test for allergen-induced basophil CD63 upregulation. The effect of cetirizine. J Investig Allergol Clin Immunol 2009; 19: 465–473.

    CAS  PubMed  Google Scholar 

  28. Singh A, Holvoet S, Weiss M, Beaumont M, Zuercher AW, Mercenier A . Increased IL-5 and IL-13 cytokine levels in ex vivo stimulated whole blood cells from grass pollen allergic donors correlate with seasonal exposure. Immunology 2011; 1: 18–23.

    CAS  Google Scholar 

  29. R Development Core Team. R: A Language and Environment for Statistical Computing 2011: R Foundation for Statistical Computing: Vienna, Austria. Computer Program.

  30. Kawase M, He F, Kubota A, Hiramatsu M, Saito H, Ishii T et al. Effect of fermented milk prepared with two probiotic strains on Japanese cedar pollinosis in a double-blind placebo-controlled clinical study. Int J Food Microbiol 2009; 128: 429–434.

    CAS  Article  Google Scholar 

  31. Ouwehand AC, Nermes M, Collado MC, Rautonen N, Salminen S, Isolauri E . Specific probiotics alleviate allergic rhinitis during the birch pollen season. World J Gastroenterol 2009; 15: 3261–3268.

    CAS  Article  Google Scholar 

  32. Isolauri E, Salminen S . Probiotics: use in allergic disorders: a Nutrition, Allergy, Mucosal Immunology, and Intestinal Microbiota (NAMI) Research Group Report. J Clin Gastroenterol 2008; 42 (Suppl 2), S91–S96.

    Article  Google Scholar 

  33. Kalliomaki M, Antoine JM, Herz U, Rijkers GT, Wells JM, Mercenier A . Guidance for substantiating the evidence for beneficial effects of probiotics: prevention and management of allergic diseases by probiotics. J Nutr 2010; 140: 713S–721S.

    CAS  Article  Google Scholar 

  34. Lagging E, van Hage-Hamsten M, Gronneberg R, Elfman L, Harfast B . Cytokine production in PBMC from allergics and non-allergics following in vitro allergen stimulation. Immunol Lett 1998; 60: 45–49.

    CAS  Article  Google Scholar 

  35. Horton DL, Remick DG . Delayed addition of glucocorticoids selectively suppresses cytokine production in stimulated human whole blood. Clin Vaccine Immunol 2010; 17: 979–985.

    CAS  Article  Google Scholar 

  36. Bradding P, Mediwake R, Feather IH, Madden J, Church MK, Holgate ST et al. TNF alpha is localized to nasal mucosal mast cells and is released in acute allergic rhinitis. Clin Exp Allergy 1995; 25: 406–415.

    CAS  Article  Google Scholar 

  37. Ying S, Robinson DS, Varney V, Meng Q, Tsicopoulos A, Moqbel R et al. TNF alpha mRNA expression in allergic inflammation. Clin Exp Allergy 1991; 21: 745–750.

    CAS  Article  Google Scholar 

Download references


We would like to thank the staff at the Metabolic Unit and Emilie Ba, and Data Manager at the Nestlé Research Center. We are grateful to Oliver Brickell, at Nestlé PTC, for all his help in the preparation of the clinical trial samples, to Dr C Blanchard for help with the IgE analysis and to Drs C Nembrini and E Eckhardt for their critical review of the manuscript.

Author information

Authors and Affiliations


Corresponding author

Correspondence to A Singh.

Ethics declarations

Competing interests

All authors are employees of Nestec S.A., which funded the work.

Additional information

Supplementary Information accompanies the paper on European Journal of Clinical Nutrition website

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Singh, A., Hacini-Rachinel, F., Gosoniu, M. et al. Immune-modulatory effect of probiotic Bifidobacterium lactis NCC2818 in individuals suffering from seasonal allergic rhinitis to grass pollen: an exploratory, randomized, placebo-controlled clinical trial. Eur J Clin Nutr 67, 161–167 (2013).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • probiotic
  • seasonal allergic rhinitis
  • IL-5
  • IL-13
  • total nasal symptom score

Further reading


Quick links